Mutagenetix > Incidental Mutations

Incidental Mutation 'R5354:Hmgcr'

423994

Institutional Source

Beutler Lab

Gene Symbol

Hmgcr

Ensembl Gene

ENSMUSG00000021670

Gene Name

3-hydroxy-3-methylglutaryl-Coenzyme A reductase

Synonyms

HMG-CoAR, 3-hydroxy-3-methylglutaryl-CoA reductase, Red

MMRRC Submission

042933-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R5354 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

96648967-96670936 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 96654896 bp

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 97 (V97M)

Ref Sequence

ENSEMBL: ENSMUSP00000132155 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022176] [ENSMUST00000168855] [ENSMUST00000169202] [ENSMUST00000170287]

Predicted Effect

probably benign
Transcript: ENSMUST00000022176
AA Change: V635M

PolyPhen 2 Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: V635M

Domain	Start	End	E-Value	Type
transmembrane domain	20	37	N/A	INTRINSIC
Pfam:Patched	56	342	2.7e-11	PFAM
Pfam:Sterol-sensing	85	234	3.4e-20	PFAM
Pfam:HMG-CoA_red	490	870	2.2e-150	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000163201

Predicted Effect

probably benign
Transcript: ENSMUST00000168855

Predicted Effect

probably benign
Transcript: ENSMUST00000169202
AA Change: V97M

PolyPhen 2 Score 0.256 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000132155
Gene: ENSMUSG00000021670
AA Change: V97M

Domain	Start	End	E-Value	Type
Pfam:HMG-CoA_red	35	219	8.8e-76	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000169945

SMART Domains

Protein: ENSMUSP00000128642
Gene: ENSMUSG00000021670

Domain	Start	End	E-Value	Type
Pfam:HMG-CoA_red	1	96	1.8e-37	PFAM
Pfam:HMG-CoA_red	96	148	2.8e-17	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000170287
AA Change: V635M

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)

SMART Domains

Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670
AA Change: V635M

Domain	Start	End	E-Value	Type
transmembrane domain	20	37	N/A	INTRINSIC
Pfam:Patched	56	347	1.4e-11	PFAM
Pfam:Sterol-sensing	85	234	7.4e-20	PFAM
Pfam:HMG-CoA_red	488	819	1.3e-148	PFAM

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.4%

Validation Efficiency

100% (80/80)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
PHENOTYPE: Inactivation of both copies of this gene results in early embryonic lethality. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A630010A05Rik	A	G	16: 14,618,671	K196R	probably benign	Het
Ablim1	T	C	19: 57,130,923	E243G	probably benign	Het
Acat1	T	A	9: 53,589,183	E271V	possibly damaging	Het
Aco1	T	C	4: 40,180,290		probably null	Het
Adam22	C	A	5: 8,090,182	G202W	probably damaging	Het
Agbl3	T	A	6: 34,814,752	H596Q	probably benign	Het
Anxa7	A	G	14: 20,464,909	L177P	possibly damaging	Het
Atp11a	A	T	8: 12,806,753	N48I	probably damaging	Het
Bcas1	T	A	2: 170,349,396	N492I	possibly damaging	Het
Bclaf1	A	G	10: 20,333,532	Y498C	probably damaging	Het
Bod1l	A	C	5: 41,831,537	V409G	probably damaging	Het
Ccdc170	G	A	10: 4,534,188	C338Y	probably benign	Het
Cdc45	C	T	16: 18,795,897	R205H	probably damaging	Het
Ckap2	A	C	8: 22,177,565	N93K	probably damaging	Het
Clca3a1	A	T	3: 144,737,005	S759R	possibly damaging	Het
Coro1c	A	T	5: 113,846,165	I347N	possibly damaging	Het
Cpox	A	G	16: 58,670,842	T139A	probably damaging	Het
Cyp4a12b	C	A	4: 115,433,464		probably null	Het
Dctn1	T	G	6: 83,183,126	V116G	possibly damaging	Het
Dhx38	A	G	8: 109,555,746	V683A	probably damaging	Het
Dnah12	G	A	14: 26,774,342		probably null	Het
Dnajb7	T	C	15: 81,408,007	E43G	probably damaging	Het
Dsc1	A	T	18: 20,087,575	V714E	probably damaging	Het
Dupd1	G	A	14: 21,677,023	R186W	probably benign	Het
Egfem1	T	C	3: 29,082,212		probably null	Het
Fchsd1	C	T	18: 37,959,873		probably benign	Het
Fmo1	T	C	1: 162,830,145	T476A	probably benign	Het
Gm10237	T	C	16: 35,920,729		noncoding transcript	Het
Gm14496	A	G	2: 182,000,809	S758G	probably damaging	Het
Gpat2	T	A	2: 127,428,723	L97Q	probably damaging	Het
Gpr162	T	C	6: 124,859,637	D357G	probably benign	Het
Hax1	A	T	3: 89,997,955	D34E	probably damaging	Het
Hsd3b2	T	C	3: 98,712,315	T105A	probably benign	Het
Ints1	A	G	5: 139,766,428		probably null	Het
Islr	T	C	9: 58,157,612	E204G	probably damaging	Het
Lrrc36	A	G	8: 105,425,364	N60D	probably damaging	Het
Maf1	T	C	15: 76,353,130		probably benign	Het
Mrgprb4	T	A	7: 48,198,329	R284W	probably benign	Het
Myh4	A	T	11: 67,255,725	N1508I	possibly damaging	Het
Nufip2	A	G	11: 77,686,277	H17R	unknown	Het
Oasl1	A	T	5: 114,936,996	I372L	probably damaging	Het
Olfr290	T	A	7: 84,916,149	Y123*	probably null	Het
Olfr414	T	C	1: 174,430,686	L86P	probably damaging	Het
Pald1	A	T	10: 61,348,661	Y226N	probably damaging	Het
Pcdhb13	G	T	18: 37,444,791	G741C	probably damaging	Het
Pcdhga10	A	G	18: 37,748,206	D340G	probably damaging	Het
Pclo	C	A	5: 14,678,808		probably benign	Het
Pcsk4	G	T	10: 80,323,689	N416K	probably damaging	Het
Pde10a	C	A	17: 8,961,980	R398S	probably damaging	Het
Plin1	T	A	7: 79,725,721	T227S	possibly damaging	Het
Pnpt1	A	G	11: 29,154,166	D542G	probably damaging	Het
Ppp4r3b	T	A	11: 29,211,646	D673E	probably benign	Het
Prr18	C	A	17: 8,341,060	P16Q	probably damaging	Het
Psmc3	T	A	2: 91,059,353	Y440N	probably damaging	Het
Rassf5	T	C	1: 131,180,648	I232V	probably benign	Het
Rims1	T	A	1: 22,538,511	D218V	probably damaging	Het
Skint10	T	C	4: 112,711,593	N309S	possibly damaging	Het
Slc6a1	T	C	6: 114,302,623	M121T	possibly damaging	Het
Slit3	A	G	11: 35,675,913	D1004G	probably damaging	Het
Snap91	C	T	9: 86,835,124	V215I	possibly damaging	Het
Son	T	C	16: 91,655,739	L458S	probably damaging	Het
St18	C	T	1: 6,844,171	A782V	probably damaging	Het
Synpo	A	G	18: 60,602,231		probably null	Het
Thbs3	A	G	3: 89,221,377	D458G	probably damaging	Het
Tpr	C	T	1: 150,445,924	R3C	probably damaging	Het
Trp63	A	G	16: 25,684,355		probably null	Het
Uhrf1bp1	G	A	17: 27,887,515	S1005N	probably benign	Het
Vmn1r27	C	A	6: 58,215,596	R141L	probably benign	Het
Wnk1	T	C	6: 119,968,523	I699V	probably benign	Het
Xkr6	A	G	14: 63,818,904	D88G	possibly damaging	Het
Zan	A	G	5: 137,380,788		probably benign	Het
Zbtb7b	T	C	3: 89,379,606		probably benign	Het
Zfp618	A	T	4: 63,080,028	D33V	probably damaging	Het

Other mutations in Hmgcr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00557:Hmgcr	APN	13	96659278	missense	probably benign
IGL01369:Hmgcr	APN	13	96666522	missense	probably null	1.00
IGL01575:Hmgcr	APN	13	96656595	missense	possibly damaging	0.56
IGL02183:Hmgcr	APN	13	96663127	missense	probably damaging	1.00
IGL02515:Hmgcr	APN	13	96666512	splice site	probably benign
IGL02716:Hmgcr	APN	13	96660012	critical splice acceptor site	probably null
IGL03278:Hmgcr	APN	13	96656762	splice site	probably benign
IGL03367:Hmgcr	APN	13	96665853	missense	probably damaging	0.98
PIT4131001:Hmgcr	UTSW	13	96659054	missense	probably damaging	1.00
PIT4504001:Hmgcr	UTSW	13	96663097	missense	possibly damaging	0.95
R0003:Hmgcr	UTSW	13	96652145	missense	probably damaging	1.00
R0017:Hmgcr	UTSW	13	96652089	splice site	probably benign
R0017:Hmgcr	UTSW	13	96652089	splice site	probably benign
R0217:Hmgcr	UTSW	13	96651980	missense	probably damaging	1.00
R0511:Hmgcr	UTSW	13	96660143	unclassified	probably null
R0707:Hmgcr	UTSW	13	96650643	unclassified	probably benign
R1301:Hmgcr	UTSW	13	96659020	missense	probably damaging	0.97
R2203:Hmgcr	UTSW	13	96656633	missense	probably damaging	1.00
R2204:Hmgcr	UTSW	13	96656633	missense	probably damaging	1.00
R2433:Hmgcr	UTSW	13	96665885	missense	probably damaging	1.00
R2938:Hmgcr	UTSW	13	96663068	missense	probably damaging	0.99
R3159:Hmgcr	UTSW	13	96665847	missense	probably damaging	1.00
R3737:Hmgcr	UTSW	13	96651063	missense	probably damaging	1.00
R3752:Hmgcr	UTSW	13	96663116	missense	probably damaging	1.00
R3837:Hmgcr	UTSW	13	96659089	missense	probably benign	0.19
R3838:Hmgcr	UTSW	13	96659089	missense	probably benign	0.19
R3839:Hmgcr	UTSW	13	96659089	missense	probably benign	0.19
R4034:Hmgcr	UTSW	13	96651063	missense	probably damaging	1.00
R4035:Hmgcr	UTSW	13	96651063	missense	probably damaging	1.00
R4210:Hmgcr	UTSW	13	96660221	missense	probably damaging	1.00
R4783:Hmgcr	UTSW	13	96666193	missense	probably damaging	1.00
R4820:Hmgcr	UTSW	13	96660192	missense	probably damaging	1.00
R5090:Hmgcr	UTSW	13	96650590	missense	probably benign
R5113:Hmgcr	UTSW	13	96656732	missense	probably benign	0.00
R5209:Hmgcr	UTSW	13	96666512	splice site	probably benign
R5571:Hmgcr	UTSW	13	96666663	missense	probably benign	0.11
R5804:Hmgcr	UTSW	13	96666187	missense	probably damaging	0.98
R5886:Hmgcr	UTSW	13	96660183	missense	probably damaging	1.00
R6340:Hmgcr	UTSW	13	96665858	missense	probably damaging	1.00
R6638:Hmgcr	UTSW	13	96658982	missense	probably benign
R6699:Hmgcr	UTSW	13	96660209	missense	probably damaging	1.00
R7024:Hmgcr	UTSW	13	96658910	missense	probably benign	0.10
R7061:Hmgcr	UTSW	13	96666148	missense	possibly damaging	0.64
R7284:Hmgcr	UTSW	13	96652665	missense	probably damaging	1.00
R7286:Hmgcr	UTSW	13	96666597	missense	probably damaging	1.00
R7705:Hmgcr	UTSW	13	96656723	missense	probably benign	0.01
R7709:Hmgcr	UTSW	13	96663097	missense	possibly damaging	0.95

Predicted Primers

PCR Primer
(F):5'- GGTGTGTACCACAGGGATATG -3'
(R):5'- GTGTATTAAAGAGTTGGTCCACC -3'

Sequencing Primer
(F):5'- AGCACAGTTATGGTCTCAGC -3'
(R):5'- AAAGAGTTGGTCCACCTTCTATTC -3'

Posted On

2016-08-04